Fetal and neonatal murine skin harbors Langerhans cell precursors
Fetal and neonatal murine skin harbors Langerhans cell precursors
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DOI：
10.1189/jlb.1004584
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发表时间：
2005-03-01
影响因子：
5.5
通讯作者：
Elbe-Bürger, A
中科院分区：
文献类型：
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作者：
Chang-Rodriguez, S;Hoetzenecker, W;Elbe-Bürger, A
成年小鼠的驻留表皮兰格汉细胞（LC）表达ADPase，主要的组织相容性复合物（MHC）II类以及CD205和CD207分子，而第一个树突状白细胞将胎儿和新生儿表皮固定在胎儿和新生儿表皮仅是Adpase（+）。在这项研究中，我们测试了树突状表皮白细胞（DEL）是末期细胞还是代表LC前体。在胎儿和新生小鼠的表皮片中，我们没有发现凋亡的白细胞，这表明这些细胞不会原位死亡。为了解决DEL是否可以引起LC，从鼠新出生的皮肤中排序的DEL是用用于从人类CD34（+）前体产生LC的细胞因子培养的。 7-14天后，DEL增殖并获得了让人联想到LC的细胞的形态和表型。与这一发现一致，我们表明新生儿表皮具有10-20倍的骑自行车MHC II类+白细胞作为成人组织的数量。为了测试LC是否可以在体内与皮肤前体区分开，我们开发了一种移植模型。由于不可能移植胎儿表皮，因此将整个胎儿皮肤接枝到成年严重的联合免疫缺陷小鼠上。与在移植时均匀缺乏供体LC相反，在2-4周后从移植物中检查表皮，发现MHC II+供体细胞（已获得CD205和CD207），因此将其作为LC资格。最后，我们提供了证据表明，内源性LC在45天的观察期内持续存在于皮肤移植物中。这些研究表明，造血前体在胚胎寿命期间播种皮肤，并会引起LC。
Resident epidermal Langerhans cells (LC) in adult mice express ADPase, major histocompatibility complex (MHC) class II, and CD205 and CD207 molecules, while the first dendritic leukocytes that colonize the fetal and newborn epidermis are only ADPase(+). In this study, we tested whether dendritic epidermal leukocytes (DEL) are end-stage cells or represent LC precursors. In epidermal sheets of fetal and neonatal mice, we found no apoptotic leukocytes, suggesting that these cells do not die in situ. To address whether DEL can give rise to LC, sorted DEL from murine newborn skin were cultured with cytokines used to generate LC from human CD34(+) precursors. After 7-14 days, DEL proliferated and acquired the morphology and phenotype of cells reminiscent of LC. In concordance with this finding, we show that neonatal epidermis harbors 10-20 times the number of cycling MHC class II+ leukocytes as adult tissue. To test whether LC can differentiate from skin precursors in vivo, we developed a transplantation model. As it was impossible to transplant fetal epidermis, whole fetal skin was grafted onto adult severe combined immunodeficient mice. As opposed to the uniform absence of donor LC at the time of transplantation, examination of the epidermis from the grafts after 2-4 weeks revealed MHC class II+ donor cells, which had acquired CD205 and CD207, thus qualifying them as LC. Finally, we present evidence that endogenous LC persist in skin grafts for the observation period of 45 days. These studies show that hematopoietic precursors seed the skin during embryonic life and can give rise to LC.